Process of producing derivatives of n-homologues of the norhydrohydrastinin.



are.

HERMAN DECKER, F HANOVER, GERMANY, ASSIGNOR T0 FARBENFABRIKEN VORM. FRIEDR. BAYER & 00., 0F ELBEEFELD, GERMANY, A CORPORATION OF GERMANY.

PROCESS OF PRODUCING DERIVATIVES 0F N-HOMOLOGUES ,OF THE NORHYDRO- HYDRASTININ.

g 134 Specilication of Letters Patent.

No Drawing.

To all whom it may concern: 7

(R meaning alkyl, R meaning hydrogen or alkyl or aryl) can be obtained by alkylizlng norhydrohydrastinin and the 'substituted derivatives of norhydrohydrastinin, by alkylizing the primary condensation products of homopiperonylamin with aldehydes, as described ln-my Patent No. 1,073,966, Sept. 23, 1913, and transforming these alkylized primary condensation products; or by alkylizing the homopiperonylamin itself, condensing the alkylhomop peronylamins with alde-' hydes to produce an alkylnorhydrohydrastinin and then transforming these compounds'thus obtained. The products thus produced are valuable intermediate compounds for therapeutic remedies.

By the term horhydrohydrastinin I mean the simple or methyl-free mother substance of the series of bodies, the methyl derivative of which (hydrohydrastinin) occurs in nature.

'for 10 minutes at 100 viscous product is dissolved in water and is In order to illustrate the new process more fully the following examples are given,

the parts being by weight Example 1: The homopiperonylamin is heated with formaldehyde and the resulting 'methylenehomopiperonylamin, which is a thick 011,15 then transformed or condensed with 20% hydrochloric acid, whereupon the norhydrohydrastinin hydrochlorid crystal lizes Patented (bet. is, was. Application filed January 2, 1913. Serial No. 739,735. 1

out. By treating this salt with alkali, free norhydrohydrastinin is obtained. It is a crystalline substance soluble in alcohol,

benzene,ether and ligroin and insoluble-in water. 100 parts of the norhydrohydrastinin are dissolved with 400 parts of benzene and heated with 72 parts of dimethyl sulfate C. The precipitated separated withthe iodid of potassium. Be-

sides the quarternary iodid, the iodid C H N0 1, in the. shape of fine yellow needles melting at 241 0., is obtained. The corresponding'crystalline hydrochlorid melts at 274 to 276 C. and the picrate which forms light yellow needles, melts at 174 to 176 0., In the process of this example the norhydrohydrastinin hydrochlorid is first obtained by the condensation of homopiperonyla-min with formaldehyde to form the methylenehomopiperonylamin and the conversion or transformation of this product into the closed ring product (norhydrohydrastininhydrochlorid') by the action of the hydrochloric acid, and from this hydrochlorid the free norhydrohydrastinin is. obtained by treatment with alkali. The norhydrohydrastinin is then alkylized with alkyl sul-.

fate to. 'give the alkyl derivatlve, which in this case is hydrohydrastinin. The hydrochloridcan be similarly employedancl converted into the methyl derivative, as described in Example 2. The reaction of this example may be represented graphically as follows:

Example 2: 100 parts of the norhydrohydrastinin hvdrochlorid, obtainable as described in Example 1, are heated under pressure with 200 parts of formaldehyde (40%) and 101 parts of hydrochloric acid (35%) for three hours at 120 C. The hydrochlorid l Norhydrohydrastinin hydrochlorid.

of hydrohydrastinin, melting at 274 to 276 C. separates in a crystalline shape. It is similar to the iodid described in Example 1. The reaction of this example maybe represented graphically as follows:

CH 0 cH,

CHs+HCOOH O cm di Hydrohydrastinin hydrochlorid.

Example 2. In the process of this example the condensation of the base with the aldehyde, the alkylation at the nitrogen atom, and the closing of the ring or molecular change into the hydrohydrastinin substance,

are all effected in one operation. The complete reaction may be illustrated graphically as follows Homopiperonylamin.

Instead of first condensing the base with formaldehyde to form the methylene derivative, it may be first converted into the methyl or other alkyl derivative and the alkyl derivatire condensed and transformed into the closed ring compound. The alkyl derivatives of homopiperonylamin are obtainable, as described in my Patent No. 1,073,966 of. September 23, 1913, from homopiperonyL CH2 o--, cm 0- I ILH-alkyl Alkyl-homopiperonylamin.

In the process of Example 3, instead of Hydrohydrastinin hydrochlorid.

amin by condensing with an aldehyde, treating the condensation product with an alkyl halid and decomposition with steam of the resulting product. In the further treatment of these alkyl derivatives the condensation with the aldehyde and the transforming or closing of the ring can be effected in one operation, as illustrated by the following graphic equations:

l I alky1+ H 0 Alkyl-norhydrohydrastinin hydrochlorid.

tives, such as the methyl-, ethyl-, derivatives 50 the homopiperonylamin, the alkyl derivacan be used in the manner just described.

.ring formation are carried out all in one operation, when homopiperonylamin itself is used as the starting material, while the condensation and ring formation take place in one operation if the homopiperonylamin is first alkylized and the alkyl derivativeis used. The three steps of alkylizing, condensing with an aldehyde, and ring formation may accordingly take place in one operation, or in two or three operations, and in different sequence, while the same ultimate result is obtained. In the accompanying claims it will be understood that these vari- 'ous steps can be performed in different orders, and I do not desire to limit myself to any particular order, or to the order in which thesteps are referred to, except in the more specific claims in which the specific order of procedure is particularly set forth.

I claim 1. The'process of producing alkyl deriva tives of norhydrohydrastinin substances from homopiperonylamin which comprises subjecting the homopiperonylamin to the following steps,-condensing with an aldehyde, closing of the chain to form a ring by condensation and alkylizing at the nitrogen atom.

2. The process of producing alkyl derivatives of norhydrohydrastinin substances from homopiperonylamin which comprises subjecting the homopiperonylamin to condensation with an aldehyde to form a condensation product, and subsequently to the steps of condensing to close the chain to form a ring and alkylizing at the nitrogen atom.

3. The process of producing alkyl derivatives of norhydrohydrastinin substances from homopiperonylamin which comprises subjecting the homopiperonylamin to condensation with an aldehyde to form a condensation product, subsequently converting the open chain of such condensation product into a ring by condensation, and alkyliz'ing the resulting nonhydrohydrastinin substance.

4. The process of producing norhydrohydrastinin substances from homopiperonylamin which comprises condensing homopiperonylamin with an aldehyde to form an open chain condensation product, and converting the open chain of the resulting condensation product into' a ring by condensation in the presence of a condensing agent.

5. The process of producing alkyl derivatives of norhydrohydrastinin substances which comprises subjecting theprimary condensation products vof homopiperonylamin and aldehydes to the following steps,closing-of the chain to form a ring by condensation and alkylization at the nitrogen atom.

6. The process of producing alkyl derivatives of norhydrohydrastinin substances which comprises subjecting the primary condensation products of homopiperonylamin and aldehydes to ring formation by condensation in the presence of a condensing agent,

and subsequently alkylizing the resulting hydrohydrastinin substance to form the alkyl-derivatives.

7. The process of producing the methyl derivative of norhydrohydrastinin which comprises subjecting homopiperonylamin to the following steps,condensation with formaldehyde, closing of the chain to form a ring by condensation and methylation at the nitrogen atom.

8. The process of producing hydrohydrastinin which comprises subjecting homopiperonylamin to the following steps,condensation with formaldehyde, closing of the chain to form a ring by condensation under the influence of hydrochloric acid, and

methylation at thenitrogen atom. a In testimony whereof I have hereunto set my hand in the presence of two subscribing witnesses.

' HERMAN: DECKER.

Witnesses MARIE Rosanna, MARIE BEHNE.

ion 5 @crrect It is hereby certified that in Letters Patent No. 1,156,134, granted October 12,

1915, upon the application of Herman Decker, of Hanover, Germany, fer an improvement in Processes of Producing Derivatives of N-Homologues of the Norhydrohydrastinin, an error appears in the printed specification requiring correction as follows: Page 3, line 61, claim 3, for the word nonhydrohydrastinin.

read norhydrohydrasttnin; and that the said Letters Patent should be read with this correction therein that the same may conform to the record of the casein the Patent omee.

Signed and sealed this 11th day of January, A. 11)., 1916,

{seen} J. T. NEON,

Acting Cemm'isse'cncr cfPateme. 

